Search Results (1,209)

Pregnancy loss affects ~15% of couples and often results from embryonic chromosomal abnormalities. Early peripheral biomarkers that signal abnormal development could improve counseling and clinical decision-making. Here, we analyzed early-pregnancy peripheral blood from patients who conceived via assisted reproduction without preimplantation aneuploidy testing. Samples were collected ≤12 weeks’ gestation for complete blood counts with differentials and multiparameter flow cytometry to quantify major lymphocyte subsets (total T, B, cytotoxic T cells, T helpers (Th), Th1, Th2, Th9, Th17, and regulatory T cells (Treg)). Participants were followed until pregnancy resolution (live birth, euploid or aneuploid miscarriage), and immune profiles were compared by outcome using the Kruskal–Wallis test. Exploratory discriminative analyses were performed with significantly different immune cell quantities. Basophils were highest in the aneuploid miscarriage group (n = 26), distinguishing them from both euploid miscarriage (n = 27) and live birth (n = 91). Th9 cells were lower in aneuploid miscarriages compared to euploid miscarriages. Th17 levels were higher in live births compared with both miscarriage groups. Additional aneuploidy-type-specific immune differences were observed. These alterations may reflect maternal immune recognition of a non-viable conceptus and localized immune activation at the fetal–maternal interface. If validated in larger cohorts, these early peripheral markers may help identify pregnancies at risk for miscarriage, particularly those involving chromosomal abnormalities. Full article

Diet is a key modulator of the gut microbiota, thereby influencing host physiology. Microbial colonization begins early in life, influenced by maternal sources, mode of birth, diet, and environmental exposures, and stabilizes into an adult-like microbiome during early childhood. This maturation yields a microbial ecosystem dominated by Firmicutes and Bacteroidetes that contributes to host physiological homeostasis. Gut microorganisms function as an integrated metabolic system that transforms dietary substrates into bioactive metabolites, including short-chain fatty acids (SCFAs), amino acid-derived compounds, and microbial lipids. These metabolites regulate glucose and lipid metabolism, intestinal barrier integrity, and immune modulation. Although many metabolic functions are conserved, their activity is shaped by diet, microbial cross-feeding, and local intestinal conditions, enabling functional specialization within the gut. Disruption of this system, known as dysbiosis, is associated with alterations in microbial diversity and metabolic output that have been linked to metabolic diseases, including obesity and related disorders. Evidence from experimental models and observational studies suggests that these associations may involve interconnected inflammatory and metabolic mechanisms, such as impaired intestinal barrier function, low-grade inflammation, and altered dietary energy harvest; however, causal relationships in humans remain incompletely understood. Beyond peripheral effects, the gut microbiome influences host metabolism via the gut–brain axis, a bidirectional network that integrates neural, endocrine, immune, and metabolic signaling. Microbiota-derived metabolites and gut hormone modulation contribute to appetite regulation, energy balance, and glucose homeostasis, while central neuroendocrine signaling can reciprocally shape the intestinal microbial niche. Collectively, these findings highlight the gut microbiome as a central regulator of host metabolism, whose disruption may contribute to the development of metabolic disease. Full article

Pertussis, caused by Bordetella pertussis, remains a public health concern despite long-standing vaccination programs. After a marked decline during the COVID-19 pandemic, a resurgence was observed in Europe and Italy, with a sharp increase in 2024. This study describes pertussis epidemiological trends in the Tuscany Region (Italy) from 2019 to 2024 to identify high-risk groups and inform prevention strategies. A retrospective population-based analysis was conducted using cases reported to the national surveillance system (PREMAL). Incidence rates were calculated using ISTAT population data, and demographic, temporal, and clinical characteristics were analyzed. Overall, 669 cases were reported (mean annual incidence rate: 3.03/100,000 (IC 95% 2.47–3.59; period incidence rate: 18.2/100,000 (IC 95% 16.81–19.56)), with 89% occurring in 2024 (16.34/100,000 (IC 95% 15.03–17.65)). No sex differences were observed, and most cases were reported in Central Tuscany (64%). Children under 15 years accounted for 87% of cases. The highest incidence was observed among 10–14-year-olds, while infants < 1 year, particularly those under 4 months, showed the highest burden in narrower age strata. Hospitalizations occurred in 12.6% of cases, decreasing substantially in 2024. The 2024 resurgence likely reflects waning immunity, disruptions to routine vaccinations during the pandemic, and reduced pathogen circulation in previous years due to containment and isolation measures related to the pandemic. Strengthening surveillance and improving booster and maternal vaccination coverage are essential to protect vulnerable populations. Full article

Dedifferentiation—the acquisition of an early developmental state—is a hallmark of cancer. However, the underlying mechanisms that lead to cancer-associated dedifferentiation are not fully understood. Transposable elements (TEs) are becoming increasingly recognised as important regulators of development and disease. The recruitment of TE sequences has played an important role in placental evolution, and TE-derived genes play critical roles in placental development. Although important biological differences exist between tumours and the placenta, the placenta shares certain features with tumours, including the capacity to invade surrounding tissue and modulate the maternal immune response. In this regard, TEs have been implicated in cancer development, and are documented to contribute to oncogenesis through multiple different mechanisms. Moreover, cancers reacquire an epigenetic landscape, which is reflective of early development, and which corresponds to increased phenotypic plasticity, including facilitating the activation of early developmental genes. Many cancers can repurpose developmental genes, including TE-associated genes, which may contribute to pathways involved in invasion and metastasis. Determining whether TE activation is a consequence of broader epigenetic reprogramming or actively contributes to dedifferentiation will be important for understanding cancer biology and may facilitate improvements in cancer diagnosis and treatment. Full article

Thrombocytopenia affects up to 10% of pregnant women and represents the second most common blood disorder during pregnancy. Its causes include immune-mediated thrombocytopenia, hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, preeclampsia (PE), and benign pregnant thrombocytopenia. Diagnosis is crucial because the cause dictates the effect on maternal health, pregnancy management, and neonatal outcomes. This narrative review examines the range of thrombocytopenia during pregnancy, primarily focusing on diagnostic evaluation, underlying pathophysiological causes, and differential diagnosis. In addition, it organizes maternal and fetal complications that might be caused by the condition, such as bleeding, preterm birth, and neonatal thrombocytopenia. Moreover, current patient management based on available evidence and clinical practice is discussed, including immunomodulatory therapies, platelet transfusions, clinical monitoring, and supportive care. A thorough and clinically guided approach to thrombocytopenia in pregnancy is indispensable for maximizing maternal and fetal outcomes and facilitating the personalization of perinatal care. Full article

Background: Maternal immune activation (MIA) during pregnancy is a known risk factor for several neurodevelopmental and psychiatric disorders, including schizophrenia. In rodent models, MIA is commonly induced using polyinosinic/polycytidylic acid (Poly(I/C)), a viral mimetic that activates Toll-like receptor 3 (TLR3) signaling and elicits an inflammatory response in both the dam and the fetuses. MIA results in various behavioral abnormalities in offspring, including deficits in social interaction. Recent studies have shown that MIA decreases the ability to maintain mitochondrial membrane potential (ΔΨm), the electrical component of the electrochemical gradient required for ATP production and alters mitochondrial protein expression in brain tissue isolated from adult offspring. Methods: In the present study, we monitor ΔΨm non-invasively in vivo using a previously published bioluminescence probe in juvenile and adult MIA offspring. We then investigated gene expression in the medial prefrontal cortex of MIA offspring by analyzing a previously published RNA sequencing dataset in combination with MitoCarta3.0, a comprehensive inventory of genes involved in mitochondrial function. Finally, we tested the hypothesis that this mitochondrial dysfunction contributes to the behavioral deficits observed in MIA offspring. Results: We have observed impaired ΔΨm maintenance in juvenile MIA offspring that persists into adulthood. Also, we found that MIA alters the expression of many genes associated with mitochondrial energy production. We demonstrated that nicotinamide riboside, a precursor to NAD⁺ known to restore ΔΨm, significantly attenuates MIA-induced social interaction deficits. Conclusions: Together, these findings highlight mitochondrial function as a promising therapeutic target for symptoms associated with schizophrenia and support the potential for drug discovery aimed at enhancing mitochondrial health. Full article

Autism Spectrum Disorder (ASD) is a developmental disorder that manifests a broad variability of phenotypes. The underlying factors contributing to the diverse presentation of autistic phenotypes remain poorly understood. Studies have shown that environmental and genetic factors could contribute to ASD. Additionally, there is a sex bias in the disorder, where the prevalence in males is higher than in females. But it is still unknown how exposure to similar risk factors can lead to different phenotypes. The three-hit theory states that the vulnerability of an individual to develop ASD is modulated by the interplay between genetic predisposition, sex, and environmental insults. To better understand this phenomenon, we investigated whether an environmental insult, via maternal immune activation (MIA) during pregnancy could influence the development of the autistic-like phenotype in a genetically predisposed mouse strain, contactin-associated protein-like 2 (CNTNAP2) knockout. CNTNAP2 knockout, sex, and maternal immune activation had significantly additive effects on repetitive/stereotyped and social behavior in the offspring, while working memory and sensory gating were not affected by hits. These results indicate that genetics, sex, and environment interact to influence autistic-like phenotypes in a behavior-specific manner. Full article

Background: Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neurological disease, including congenital Zika syndrome (CZS) following utero infection and Guillain–Barré syndrome in adults. The 2015–2016 epidemic in the Americas highlighted the profound maternal and neonatal consequences of ZIKV infection. Although reported transmission has declined, ongoing circulation of competent vectors and population susceptibility sustain a substantial risk of future outbreaks, underscoring the need for effective vaccines. Methods: We developed a recombinant Modified Vaccinia Ankara (MVA)-based vaccine candidate expressing the ZIKV pre-membrane (prM) and envelope (E) proteins and evaluated its immunogenicity and protective efficacy in interferon receptor-deficient AG129 mice. Results: Vaccination induced strong humoral and cellular immune responses and conferred significant protection against viral replication in key target organs, including the brain and testes, following ZIKV challenge. Conclusions: These preclinical findings support further development of this MVA-based ZIKV vaccine as a promising strategy to prevent ZIKV infection and its associated neurological complications. Full article

Normal pregnancy is associated with uterine and vascular remodeling by matrix metalloproteinases (MMPs) to facilitate placental blood flow and uterine expansion for the growing fetus. Increases in MMP-2 and MMP-9 in response to estrogen and progesterone promote placentation, uteroplacental vascularization and fetal growth during healthy pregnancy, but are altered in preeclampsia (PE). PE is characterized by hypertension in pregnancy (HTN-Preg) and fetal growth restriction (FGR). Predisposing genetic, demographic and environmental factors alter uteroplacental MMPs, immune response and integrins leading to apoptosis of invasive trophoblasts, inadequate spiral arteries remodeling, and reduced uteroplacental perfusion pressure (RUPP). Ensuing placental ischemia causes imbalance between anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and pro-angiogenic placental growth factor (PlGF) and promotes the release of tumor necrosis factor-α (TNF-α), hypoxia-inducible factor, reactive oxygen species, and angiotensin AT₁ receptor agonistic autoantibodies. Systemically, these bioactive factors target vascular endothelial cells, smooth muscle cells, and extracellular matrix, causing endothelial dysfunction, vasoconstriction, inadequate vascular remodeling, and HTN-Preg, while locally they diminish uteroplacental remodeling and cause FGR. In support, animal models of HTN-Preg induced by RUPP or infusion of sFlt-1 or TNF-α show decreases in vascular MMP-2, MMP-9 and vasodilation, increases in MMP-1, MMP-7 and vasoconstriction, collagen accumulation, and arterial stiffness. Also, decreases in uterine MMP-2 and MMP-9 could impede uterine expansion and lead to preterm birth. Conversely, PlGF and TNF-α antagonist reversed MMPs imbalance and collagen accumulation, and improved vascular function, blood pressure, and pup weight in HTN-Preg models. Persistent postpartum changes in MMPs could affect maternal hemorrhage, future pregnancies, and HTN, and cause fetal programming of cardiovascular and metabolic diseases. Understanding the aberrant uteroplacental and vascular signaling and remodeling by MMPs could help design new biomarkers and remedies for PE. Targeting bioactive factors and rectifying MMP imbalance could improve vascular and uteroplacental remodeling, and manage HTN-Preg, FGR and PE. Full article

Background: Gestational diabetes mellitus (GDM) and periodontitis (PD) are chronic inflammatory conditions that may share metabolic and immune pathways. Evidence suggests an association between them, although results across studies remain inconsistent. This systematic review and meta-analysis evaluated the relationship between GDM and PD and examined whether GDM influences key periodontal parameters. Methods: A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and Embase was conducted up to August 2025 following PRISMA guidelines. Observational studies comparing periodontal status in pregnant women with and without GDM were included. Periodontal status was assessed using probing pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP). Study quality was evaluated with the Newcastle–Ottawa Scale, and random-effects models were applied to estimate pooled associations. Results: Fifteen studies involving about 3800 pregnant women met the criteria. A significant association was found between GDM and PD (Odds Ratio [OR] 2.10; 95% Confidence Interval [CI] 1.64–2.69). No significant association emerged between GDM and gingivitis. Women with GDM showed increased BOP and higher PPD, indicating greater periodontal inflammation, while CAL did not significantly differ between groups. Conclusions: The findings support a significant association between GDM and periodontitis, suggesting that gestational hyperglycemia may enhance periodontal inflammation and early tissue changes. Incorporating periodontal screening into prenatal care may benefit maternal oral and metabolic health. Further longitudinal and interventional studies are needed to clarify causality and to explore whether periodontal therapy may help reduce risks linked to GDM. Full article

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in infants and young children worldwide and continues to impose a substantial disease burden despite recent advances in preventive strategies. Natural infection does not confer durable protective immunity, resulting in repeated reinfections, with the most severe disease occurring during early infancy. This review examines antibody-mediated prevention of RSV infection, with particular emphasis on vaccine development and maternal immunization. We reviewed current evidence on RSV pathogenesis, immune evasion, and antigenic characteristics relevant to vaccine design, focusing on viral surface glycoproteins targeted by preventive strategies. Recent data on licensed vaccines, long-acting monoclonal antibodies, and maternal immunization approaches were also evaluated. The RSV fusion (F) glycoprotein is the principal target of neutralizing antibodies and underpins currently licensed vaccines and monoclonal antibody products. Although circulating RSV strains show gradual antigenic evolution, primarily in the attachment protein, the F protein remains relatively conserved, resulting in only modest reductions in neutralization by human polyclonal sera over time. Constrained evolution of the F protein likely contributes to the sustained effectiveness of F-based interventions. However, waning F-specific neutralizing antibody titers contribute to susceptibility to reinfection, underscoring the importance of passive immunization strategies during early life. Maternal vaccination and long-acting monoclonal antibodies represent key advances in protecting young infants against RSV, but challenges remain in achieving equitable global implementation. Continued evaluation of antigenic evolution, the durability of protection, and optimization of maternal and infant immunization strategies will be critical for long-term disease control. Full article

This study investigated the effects of tributyrin supplementation on the immune and antioxidant status of lambs born to perinatal Hu ewes with negative energy balance (NEB) at 75%. Twenty healthy Hu ewes (average body weight 45.00 ± 5.00 kg) with similar body condition score, pregnant for 100 days with twin lambs, were randomly allocated into two groups: NEB group and 0.5% tributyrin supplementation group (TB). Lambs were artificially fed with milk from their respective maternal groups for 42 days and were classified as L-NEB (n = 20) and L-TB (n = 20). The experimental period lasted from 40 days before delivery to 42 days after delivery. At 42 days of age, five male lambs from each group were randomly selected and euthanized for analysis. Tributyrin supplementation significantly increased fat-corrected milk yield, milk fat content, and colostrum fat yield in perinatal ewes (p < 0.01). Lambs in the L-TB group exhibited improved growth performance compared with L-NEB lambs (p < 0.05). Serum triglyceride concentration at 7 days of age was 68.4% higher, and serum triglyceride and glucose concentrations at 42 days of age were 42.9% and 13.9% higher, respectively, in the L-TB group than in the L-NEB group (p < 0.05). In addition, the L-TB group showed a 39.2% lower serum IL-1β concentration at 7 days and significantly downregulated hepatic IL-8 mRNA expression at 42 days, together with enhanced antioxidant capacity (p < 0.05). These findings suggest that dietary tributyrin supplementation at 0.5% in perinatal undernourished ewes, applied under a controlled NEB feeding regimen, may improve milk composition and, consequently, enhance growth performance, immune status, and antioxidant capacity in lambs. Full article

Background/Objectives: Early-life gut colonization is crucial for immune system development and metabolic programming. Lactobacillus reuteri has been investigated for its capacity to modulate neonatal gut microbiota, but evidence regarding maternal supplementation during lactation remains limited. This study aimed to evaluate the effect of maternal supplementation with L. reuteri SGL 01 on the microbial composition of breast milk and neonatal feces over the first month of life. Methods: This is an exploratory, prospective, open-label randomized clinical trial. Lactating mothers of full-term and exclusively breastfed infants were randomized to receive either daily L. reuteri SGL 01 (1 × 10⁹ CFU) for 30 days or no supplementation. Quantitative real-time PCR was used to assess Bifidobacterium spp., Lactobacillus spp., Clostridium spp., and the Bacteroides fragilis group in maternal milk and neonatal feces at baseline (T0) and after 30 days (T1). Results: Twenty-seven mother–infant dyads completed the study (15 supplemented, 12 controls). No significant changes in breast milk microbiota composition were observed across any of the bacterial taxa following maternal supplementation. In contrast, neonatal fecal samples from the supplemented group showed significant increases in Bifidobacterium spp. (p < 0.001), Lactobacillus spp. (p = 0.029), and Clostridium spp. (p = 0.003) at T1. No significant microbial changes were observed in the control group, except for a slight reduction in Clostridium spp. (p = 0.046). Conclusions: Maternal supplementation with L. reuteri SGL 01 did not modify breast milk microbiota but was associated with a modulation of neonatal gut colonization, including an increased abundance of beneficial taxa such as Bifidobacterium, suggesting potential indirect maternal-to-infant microbial effects. Full article

Chronic kidney disease (CKD) represents a major global health burden, with growing evidence indicating that its origins extend back to early developmental stages. This narrative review integrates epidemiological, clinical, and mechanistic experimental evidence to position inflammation as a life-course driver of kidney vulnerability rather than a late-stage consequence. Inflammation has emerged as a central mechanistic link connecting adverse prenatal and postnatal exposures to lifelong kidney vulnerability. We highlight the translational potential by identifying pathways amenable to early-life interventions that could modify disease trajectory. During fetal development, maternal nutritional status, metabolic stress, and inflammatory exposures influence nephron endowment, immune maturation, and epigenetic regulation, thereby shaping long-term CKD risk. In childhood, early immune dysregulation and low-grade inflammation contribute to disease initiation, defining critical windows for preventive and renoprotective interventions that can be implemented in at-risk populations. In adulthood and aging, persistent activation of cytokine signaling, inflammasomes, oxidative stress pathways, autophagy–mitophagy imbalance, and cellular senescence drives progressive kidney injury, further amplified by gut microbiota dysbiosis and renin–angiotensin system interactions. Emerging life-course strategies include maternal nutrition optimization, early-life risk stratification, targeted anti-inflammatory and immunomodulatory therapies, and microbiota-directed interventions tailored to developmental stage and individual risk profile. By emphasizing inflammation as a developmentally programmed and preventable process, this review underscores opportunities for early-life and transgenerational CKD prevention, translating mechanistic insights into actionable strategies for preventive medicine and public health. Full article

Recognition and binding to β-galactose-containing carbohydrates and lipids are crucial for several fundamental biological processes that are mediated primarily by a family of proteins known as galectins (S-type lectins). Galectins in the human placenta regulate critical processes such as maternal–fetal immune tolerance, trophoblast invasion, vascular remodeling and angiogenesis, ensuring proper fetal development and preventing pregnancy complications such as preeclampsia and miscarriage. Gestational diabetes mellitus (GDM) is a widespread complication of pregnancy, affecting approximately 1 in 7 pregnancies, and its incidence is increasing globally, indicating a particularly strong association with the obesity pandemic. Profiles of placental expression and distribution of individual galectins significantly change during the course of GDM. This is accompanied by placental dysfunction, which is especially severe with poor glycemic control. The aim of this review is to present the current state of knowledge on the involvement of abnormal galectin signaling in the pathomechanisms of GDM-associated placental dysfunction. Further research is needed to determine whether changes in placental galectins occur secondary to metabolic abnormalities in GDM or are involved as a primary cause. Galectins present in placental tissue and serum should be validated as potential biomarkers of GDM. Full article